Tan and colleagues tested
the activity of a variety of antiviral agents against a Singapore strain of
SARS coronavirus grown in Vero cells. No inhibition of cytopathic effect was
found when the following drugs were used: acyclovir, ganciclovir, indinavir,
nelfinavir, saquinavir, lamivudine zidovudine, oseltamivir, zanamivir, amantadine,
foscarnet, interferon a-2a, interferon a-2b, and
interferon b-1a. Complete inhibition of cytopathic effects was noted
with interferon a-n1 (Wellferon), interferon a-n3 (Alferon), and
interferon b-1b (Betaferon). Ribavirin exerted an effect only at concentrations
that produced direct cytotoxicity.

Comment by Stan Deresinski,
MD, FACP

Many patients with SARS
have been treated with a combination of ribavirin and corticosteroids. However,
this and previous studies have failed to demonstrate clinically useful activity
of ribavirin as a single agent in vitro. Neither agent has been demonstrated
to be effective in clinical trials, and both have potential toxicities.

This study indicates that
certain interferon preparations may have potential as therapeutic agents in
patients with SARS. However, some of the results conflict with those previously
reported. For instance, investigators at Fort Detrick found that recombinant
interferon b-1a inhibited SARS coronavirus replication in vitro.1
Consistent with the finding of in vitro activity with the non-pegylated form
of this molecule,2 pegylated interferon a, given prophylactically,
significantly reduced viral replication and excretion, as well as pulmonary
damage, in experimentally infected macaques.3

The combination of corticosteroids
and interferon alfacon-1 (Infergen) has been reported to improve outcomes relative
to patients given corticosteroids alone in an open-label study.4
This consensus interferon was not evaluated by Tan et al. It differs from interferon
a-2a and interferon a-2b by 18-19 amino acids, with changes at 2 of 3 interferon-binding
sites.

Immunological approaches
to treatment and prevention of SARS are also under investigation. A human monoclonal
antibody to the S1 domain of the spike protein involved in binding to cellular
receptors is an effective inhibitor of SARS coronavirus cell entry.5
This finding also suggests that a vaccine that elicits antibody that binds to
this site may potentially be protective against SARS. In fact, a DNA vaccine
encoding the viral-spike glycoprotein induces neutralizing antibody and protective
immunity in mice.6 An adenoviral-based vaccine eliciting a response
to the spike protein also has been demonstrated to elicit neutralizing antibody
in rhesus macaques.7